Fluoride ion releasing dental materials

ABSTRACT

Described are novel fluoride ion-releasing acrylic or methacrylic acid-based monomers, fluoride ion-releasing dental resin materials prepared from the monomers, and processes for preparing the monomers and dental resin materials. The monomers of the invention are prepared in good yield from readily available starting materials. Dental resin materials of the invention exhibit excellent sustained fluoride ion release.

BACKGROUND

This invention pertains to novel fluoride ion-releasing polymerizableacrylic and methacrylic acid derivatives, and to their preparation anduse in fluoride-ion releasing resins which have use in dentalapplications.

The fluoride ion has long been recognized as an effective agent forreducing carious attack and demineralization of tooth structure. Forthis reason, there has been interest in incorporating fluoride ion indental materials.

The most widely used fluoride-containing substances added to dentalresin materials are sodium fluoride, stannous fluoride, and certainammonia fluorides. Attempts have been made to incorporate such inorganicfluoride salts into cavity liners, sealants, coatings, orthodonticbracket adhesives and amalgams. However, a primary problem withincorporation of inorganic fluoride-containing salts into dental resinsis an inherent incompatibility caused by a large difference in polaritybetween the ionic fluoride salt and the low-polarity dental resin, thelatter being an organic material. Incompatibility usually causes phaseseparation with the resin, loss of mechanical integrity of the resin andrapid fluoride ion release within the first few hours of use.Incorporation of low molecular weight organic fluoride species has aplasticizing effect which leads to similar undesirable results.

Kadoma et al., Macromol. Chem. 1981, 182, 273 and Macromolecules 1982,15, 1119, synthesized a fluoride ion releasing methacryloylfluoride-methylmethacrylate copolymer, in which the fluorine iscovalently bonded to a carbonyl group. This resulted in the slow releaseof the fluorine as fluoride ion by hydrolysis of the acid fluoride inaqueous solution. It has been shown that this copolymer can beincorporated into experimental sealants and will release fluorideslowly. Tanaka et al., J. Dent. Res. 1987, 66, 1591; and Nishida et al.,JP 62-012,706 (1987).

Rawls et al., U.S. Pat. No. 4,515,910 (1985) and U.S. Pat. No. 4,572,920(1986), incorporated fluoride ion as a mobile charge into an acrylicanion exchange resin. These studies demonstrated that t-butylaminoethylmethacrylate hydrogen fluoride can be copolymerized readily with otheracrylic monomers and can serve as a source of fluoride ion in the finalresin. These resins were tested as fissure sealants, orthodontic cementsand resin materials.

In light of this background there remains a need for further compoundswhich can be used in the preparation of fluoride ion-releasing dentalmaterials. Desirably, the compounds would be prepared from readilyavailable starting materials, and provide dental materials withacceptable levels of sustained fluoride ion release while exhibitingacceptable hardness and resistance to deterioration. The presentinvention addresses these needs.

SUMMARY OF THE INVENTION

The present invention provides novel polymerizable, fluorideion-releasing monomers, methods for their preparation and use, anddental resin compositions prepared from the novel monomers. Accordingly,one preferred embodiment of the invention provides fluoride-releasingacrylamide or methacrylamide monomers bearing ion-exchange or chelationsites carrying fluoride ion or a fluoride-containing anion, whichexhibit superior stability over related esters in aqueous and otherenvironments in which they are employed. Preferred such monomers areencompassed by the general formula (I): ##STR1## wherein Y⁻ is fluorideor a fluoride-containing anion, R¹ is --H or methyl, R² is a divalent C₁-C₁₂ alkylene radical, and each R³, which may be the same as or maydiffer from one another, is H, a C₁ -C₁₆ alkyl or hydroxyalkyl, or agroup of the formula (II), (III) or (IV): ##STR2## wherein R¹, R² and R³are as defined above, n is an integer from 1 to 12, preferably 2 to 6,and each R⁴, which may be the same as or may differ from one another, isH; lower alkyl or lower hydroxyalkyl (including mono- andpolyhydroxyalkyl) such as hydroxymethyl, 1,2 -dihydroxyethyl,hydroxypropyl, for example 2,3-dihydroxypropyl (e.g. --CH₂ CHOHCH₂ OH)or 1,3-dihydroxypropyl (e.g. --CH(CH₂ OH)₂) , hydroxybutyl, for exampletris (hydroxymethyl)methyl (i.e. --C(CH₂ OH)₃); or an amide group of theformula --CH(CH₂ OH)(CONHCH₂ CH₂ OH).

Another preferred embodiment of the invention provides a polymerizablemonomer, preferably an acryic or methacrylic acid-based monomer, bearingan anion exchange site carrying a protonated, fluoride-containing anionof the formula ((HF)_(x) F)-- wherein x is an integer from 1 to about 7.Monomers carrying such protonated, fluoride-containing anions exhibitsuperior chemical stability as compared to corresponding monomerscarrying the simple fluoride ion (F⁻⁻).

Another preferred embodiment of the present invention provides a dentalresin material comprising a reaction product of a monomer of theinvention as specified above, with at least one other acrylate ormethacrylate monomer, with the proviso that at least one of the reactedmonomers is a crosslinking agent (i.e. has at least two polymerizablegroups in the molecule). In accordance with one aspect of the invention,the crosslinking agent itself can carry one or more fluoride ions orfluoride-containing anions such as those of the formula ((HF)_(x) F)--wherein x is as defined above.

Another preferred embodiment provides a fluoride ion-releasingpolymerizable monomer, preferably an acrylic or methacrylic acid-basedmonomer, bearing a chelation site carrying fluoride or afluoride-containing anion. In such monomers, the chelation of thefluoride or fluoride-containing anion, for example promoted by hydrogenbonding, will enable resins formed from the monomers to release fluorideions over time.

Another preferred embodiment of the invention provides a method forpreparing a dental resin material which comprises the step ofcopolymerizing a monomer of the invention as specified above with atleast one other acrylic acid or methacrylic acid-based monomer, with theproviso that at least one of the reacted monomers is a crosslinkingagent.

Still another preferred embodiment of the invention provides a methodfor preparing an acrylamide or methacrylamide monomer of formula (I).The method comprises reacting a compound of the formula: ##STR3## with acompound of the formula R³ -L, wherein R¹, R² and R³ are as definedabove and L is a leaving group such as Cl, Br, I or an alkylsulfonate orarylsulfonate (i.e. SO₃ R wherien R is alkyl or aryl), to thereby form acompound of the formula: ##STR4## and exchanging L⁻ for fluoride or afluoride-containing anion, so as to prepare a fluoride-releasing monomerof formula (I). In a preferred mode, the exchange is achieved bycontacting the monomer (VI) with an anion-exchange resin loaded with afluoride or fluoride-containing anion.

The invention provides novel fluoride ion-releasing monomers that may beeffectively polymerized along with other monomers to prepare fluorideion-releasing dental resin materials. The novel fluoride ion-releasingmonomers can be prepared from relatively inexpensive and readilyavailable starting materials in good yield. Advantageously, dental resinmaterials prepared using the inventive monomers have excellent sustainedlevels of release of fluoride ion and demonstrate acceptable hardness,durability and other physical and chemical characteristics.

Additional embodiments, features and advantages of the invention will beapparent from the description which follows.

DESCRIPTION OF THE PREFERRED EMBODIMENT

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to certain embodiments thereof andspecific language will be used to describe the same. It willnevertheless be understood that no limitation of the scope of theinvention is thereby intended, such alterations and furthermodifications of the principles of the invention as described hereinbeing contemplated as would normally occur to one skilled in the art towhich the invention relates.

The invention provides acrylic- or methacrylic acid-based dental resincompositions which deliver fluoride when bonded in place on dentalsurfaces without degradation of the resin composition. Acrylic- ormethacrylic acid-based dental resin compositions are well known andwidely used. The compositions of the invention are acrylic- ormethacrylic-based compositions, which are the reaction products of anumber of components. A first component is a conventional acrylic ormethacrylic acid-based monomer, typically an acrylic or methacrylic acidester. Conventionally, the alkyl radical of the acrylic or methacrylicester contains about 1 to 12 carbon atoms ("a C₁ to C₁₂ alkyl group"),and even more conventionally is a C₁ to C₅ alkyl group. Other estergroups can be used, to the extent that they do not detrimentallyinterfere with the particular properties desired of the final resin.

Representative known acrylates and methacrylates which may be utilizedthus include those in which the alkyl radical of the ester group ismethyl, ethyl, isopropyl, butyl, capryl, palmityl, stearyl, lauryl,bis-glycidyl, 2-hydroxyethyl, 1,3-butylene glycol, and the like. Otherderivatives of acrylic and methacrylic acid which are suitable for usein the invention include various bisphenol A derivatives of acrylic andmethacrylic acid such as those noted in the above-cited patents to Rawlset al., such as 2,2-Bis[4-methacryloyloxyphenyl]propane;2,2-Bis[4-(2-methacryloyloxy-ethoxy)phenyl]propane;2,2-Bis[4-(3-methacryloyloxy-propoxy-phenyl]propane; the dimethacrylatederivative of 1,2-cyclohexanedicarboxylic acid; the dimethacrylatederivative of 4-cyclohexene-1,2-dicarboxylic acid; and dimethacrylatemonomers containing urethane groups such as UEDMA and TUDMA.

The reaction product will generally include a crosslinking monomer whichhas at least two polymerizable groups per molecule. The crosslinker maybe conventional or may be a crosslinking monomer of the invention asdescribed herein. Representative conventional crosslinking monomers thatmay be used in the invention include, for example, dimethacrylatemonomers such as ethylene glycol dimethacrylate, trimethyleneglycoldimethacrylate, and polyethyleneglycol dimethacrylate.

The reaction product of the invention also includes a novelfluoride-releasing monomer of the invention. In one preferred embodimentan inventive acrylamide or methacrylamide monomer may be used which isencompassed by the formula (I): ##STR5## wherein Y⁻ is a fluoride orfluoride-containing anion, R¹ is --H or methyl, R² is a divalent C₁ -C₁₂alkylene radical, suitably a lower alkylene radical (i.e. C₁ to aboutC₆), and each R³, which may be the same as or may differ from oneanother, is H, C₁ -C₁₆ alkyl or hydroxyalkyl (including mono- andpolyhydroxyalkyl), or a group of the formula (II), (III) or (IV):##STR6## wherein R¹, R² and R³ are as defined above and each R⁴, whichmay be the same as or may differ from one another, is H; lower alkyl(i.e. C₁ to C₆) or lower hydroxyalkyl (including mono- andpolyhydroxyalkyl) such as hydroxymethyl, 1,2-dihydroxyethyl,hydroxypropyl, for example 2,3-dihydroxypropyl (e.g. --CH₂ CHOHCH₂ OH)or 1,3-dihydroxypropyl (e.g. --CH (CH₂ OH)₂), hydroxybutyl, for exampletris(hydroxymethyl)methyl (i.e. --C(CH₂ OH)₃); or a group of the formula--CH(CH₂ OH) (CONHCH₂ CH₂ OH). Advantageously, where at least one groupR⁴ contains two or more hydroxyl or amino functions, or a combinationthereof, the inventive monomer can contain a chelating moiety forchelating fluoride ions, as opposed to or in addition to an ion-exchangesite. Thus, another broad aspect of the invention provides apolymerizable monomer such as an acrylic acid or methacrylic acid-basedmonomer bearing a chelation site carrying a fluoride orfluoride-containing anion. As indicated above, the chelation site willtypically be provided by an organic moiety (e.g. having up to about 20carbon atoms, preferably up to about 10 carbon atoms) containing two ormore nitrogen (N) or oxygen (O) containing groups, for example hydroxyland/or amino functions, which is effective to chelate a fluoride orfluoride-containing anion.

In accordance with one aspect of the invention, one or more monomers offormula (I) will be included in the overall reaction mixture in order toprovide a caries-inhibiting amount of fluoride release from the resin.Preferred are monomers (I) wherein R² is --(CH₂)m wherein m is 2 to 6,and/or wherein two of the groups R³ are lower alkyl such as methyl orethyl. Advantageously, where at least one group R³ is of formula (II) or(III), the inventive monomer can serve as a crosslinking agent. Anotherpreference exists when two groups R³ are lower alkyl groups such asmethyl or ethyl and the third group R³ is methyl, ethyl, or a polargroup such as a hydroxyalkyl or amido group of formula (IV). These loweralkyl and polar groups have been found to provide monomers which formharder resins which effectively release fluoride over an extended periodof months.

Inventive fluoride-releasing monomers can be prepared by a series ofsteps including reacting a compound of the formula: ##STR7## with acompound of the formula R³ --X, wherein R¹, R² and R³ are as definedabove, and wherein L is a leaving group such as --Cl, --Br, --I or--SOBR wherein R is alkyl such as C₁ to C₁₆ alkyl, aryl such as phenylor lower-alkyl-substituted phenyl (e.g. toluenesulfonate such asp-toluenesulfonate), or combined alkyl-aryl, to form a compound of theformula: ##STR8## and exchanging L⁻⁻ for a fluoride ion or afluoride-containing anion. This exchange is preferably accomplished bycontacting (VI) with an anion-exchange resin loaded with the desiredfluoride or fluoride-containing anion. For example, the anion-exchangeresin can be a polymer containing aliphatic quaternary ammoniumfunctions, such as appropriate Amberlite™ resins (e.g. IRA-400)commercially available from Rohm & Haas, or a polymer containingpyridine functions, for example a Reillex™ crosslinkedpoly(vinylpyridine) resin available from Reilly Industries, Inc. ofIndianapolis, Ind., including Reillex™ 425 resin which is apoly(4-vinylpyridine) resin crosslinked with 25% divinylbenzene.

The ion-exchange resin can be loaded with fluoride, for example, bycontacting the resin with an aqueous solution of sodium fluoride. Theion-exchange resin can be loaded with a fluoride-containing polyatomicanion, in particular a protonated fluoride ion of the formula ((HF)_(x)F)⁻ wherein x is an integer from 1 to about 7, by contacting the resinwith liquid hydrogen fluoride or a solution of hydrogen fluoride in anaqueous solvent, more preferably an alcohol/water solvent. Preferredalcohols for these purposes include lower alcohols (i.e. those having 1to about 6 carbon atoms) and especially methanol and ethanol. The valuefor x in the above-defined protonated fluoride-containing anionincreases with increasing hydrogen fluoride concentration and/orincreasing contact time of the hydrogen fluoride solution with theresin. Thus, the value for x can be controlled as desired by increasingor decreasing the hydrogen fluoride concentration of the solution and/orits contact time with the resin to be loaded. Similarly, after loading,rinsing with an aqueous solution, for example water or a water/alcoholrinse, or with an alcoholic solution, will decrease the value for x. Inpreferred work to date, the value for x has been 2 or 3.

The loaded ion exchange resin can be contacted with theion-exchangeable, potential fluoride-bearing monomer, for example offormula (VI), by suspending the resin in solution with the monomerand/or by passing a solution of the monomer, for example in an alcohol,through a resin column containing the loaded resin. In either case thecontact leads to an ion exchange whereby the monomer eluting from theresin column carries the fluoride or fluoride-containing anion (Y⁻) andthe original counterion (L⁻) of the monomer remains on the resin.

The applicants' discovery of the improved chemical stability of resinsand resin precursors provided by the anion ((HF)_(x) F)⁻ also providesmeans for improving fluoride-bearing polymerizable monomers generally,for example including the ester-based monomers described in theabove-cited Rawls et al. patents. This aspect of the invention thusbroadly provides an acrylate or methacrylate monomer bearing anion-exchange site carrying a protonated fluoride anion of the formula((HF)_(x) F)⁻ wherein x is an integer from 1 to about 7, more typicallyfrom 1 to about 5 and preferably from 2 to 3. As indicated, monomerscarrying this anion have exhibited superior stability relative tocorresponding monomers which carry the fluoride ion, while neverthelessdemonstrating the capacity to successfully form resin materials whichrelease fluoride ion over time.

To form a resin for use as a dental resin material, the above-describedcomponents, optionally in the presence of other components which may beconventional, are reacted in the presence of a free radical initiator.The resulting dental resin material releases fluoride ion slowly whilenot itself undergoing significant degradation.

In one mode of use, one or more components are first combined with aninitiator while one or more other components, or additional amounts ofthe same components, are combined with an accelerator. When, thereafter,the initiator-containing mix is blended with the accelerator-containingmix, the polymerization occurs and the dental resin is formed. In thisregard, suitable initiators and accelerators which can be used inacrylic- or methacrylic-based polymerizations are well known. Suitableinitiators include, for instance, peroxides such as benzoyl peroxide,cumene hydroperoxide, and the like. Representative suitable acceleratorsinclude N,N-dimethyl-p-toluidine, dihydroxy ethyl-p-toluidine,1-acetyl-thiourea, and the like. However, as indicated, suitableinitiators and accelerators are in general well known and their use inthe invention is well within the purview of the ordinarily skilledartisan.

Of course, additional ingredients are conventionally employed inacrylic- or methacrylic-based dental resin compositions and may beemployed in the present invention as well. These include for instancefillers such as inorganic silicates, amorphous silica, glass, quartz,alumina, apatite phosphates and the like, polymerization inhibitors suchas hydroquinones, e.g. butylated hydroxy toluidine, butylated hydroxyanisole and methyl ether of hydroquinone.

The following Examples are offered by way of illustration and not by wayof limitation. In the Examples, all percentages are percentages byweight unless otherwise indicated.

EXAMPLE 1 Dodecyl monomer

3-(Methacryloylamino)propyldimethylamine (8.9 g, 0.05 mol) and dodecylbromide (14.9 g, 0.06 mol) were dissolved in 50 ml of CH₃ CN. Themixture was stirred at room temperature. After 48 hours the solvent wasevaporated under vacuum. The 25 solid residue contained about 100%alkylated methacrylic monomer with bromide anion (by ¹ H-NMR analysis).Fluoride ion exchange was performed by passing a methanol solution ofthe bromide salt through a column packed with the loaded form of Reillex425 polymer (commercially available from Reilly Industries, Inc.,Indianapolis, Ind.), which was loaded with the fluoride anion ((HF)_(x)F)⁻ wherein x=2 by the following procedure. Reillex 425 resin wastreated with portions of 1N aqueous NaOH solution until no bromide orchloride ion could be detected with acidic AgNO₃ solution. Next, thecolumn was washed with de-ionized water until neutral to pH paper,collected on a Buchner funnel and washed with three resin volumes ofmethanol. The resin was transferred to a standard chromatography columnand treated with 0.5-1.0N HF solution (prepared by dilution ofcommercial 48-50% hydrofluoric acid with methanol) until the pH of theeffluent was 3-4. The resin bed was finally rinsed with one columnvolume of methanol before use. The3-(methacryloylamino)-propyldimethyldodecylammonium polyhydrogenfluoride-fluoride was purified by recrystallization from acetone. Thefluoride product is a white solid, m.p.=113°-118° C. The monomers werecharacterized by ¹ H-NMR (multiplicity, J. (Hz), area, assignment)(Solvent: CD₃ OD) ¹ H: δ 0.79 (t, 6, 3, CH₃), 1.19 (br, s, 15, 16, CH₂),1.26 (m, 10, 2, CH₂), 1.62 (m, 15, 2, CH₂), 1.84 (s, 3, CH₃), 1.87 (m,2, CH₂), 2.97 (s, 6, CH₃), 3.2 (m, 4, CH₂), 5.29 (s, 1, C═CH), 5.68 (s,1, ═CH); IR, (cm⁻¹, intensity, assignment); (728, s, br,), (933, s,C═CH₂), (1474, m, CH₂ --N), (1614, s, C═C), (1663, s, amide), (2927, s,CH₂ in alkyl chain) and elemental analysis: Found (%): C, 60.36, H10.91, N 6.72, F 13.82, Br undetectable.

EXAMPLE 2 Ethyl monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with ethyl bromide. The resulting product,3-(methacryloylamino)propyldimethyl-ethylammonium polyhydrogenfluoride-fluoride monomer, was a crystalline solid having a meltingpoint of 73°-78° C.). ¹ H-NMR analysis yielded the following results:(Solvent: CD₃ OD) ¹ H: δ 6.1, 5.7 (s, 2H, CH₂ ═), 3.7 (m, 6H, NCH₂), 3.4(s, 6H, N(CH₃)₂), 2.3 (m, 2H, CH₂, 2.2 (s, 3H, CH₃), 1.6 (t, a3H, CH₃).Similarly, ¹³ C NMR: 8 8.3, 18.3, 23.7, 37.6, 50.7, 60.6, 62.5, 121.0,140.9, 171.4.

EXAMPLE 3 Butyl monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with butyl bromide. The resulting product,3-(methacryloylamino)propyldimethyl-butylammonium polyhydrogenfluoride-fluoride monomer, was a crystalline solid having a meltingpoint of 92°-96° C. ¹ H-NMR analysis yielded the following results:(Solvent: CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H, CH₂ ═), 3.4 (m, 6H, NCH₂ ),3.1 (s, 6H, N(CH₃)₂), 2.0 (m, 2H, --CH₂ --), 1.95 (s, 3H, --CH₃), 1.7(m, 2H, NCH₂ --CH₂ --), 1.4 (t, 2H, NCH₂ CH₂ --CH₂ --), 1.0 (t, 3H,CH₃), ¹³ C: δ 13.9, 18.8, 20.6, 23.8, 25.4, 37.6, 51.4, 62.9, 65.0,121.1, 140.9, 171.4. Elemental analysis: Found (%)C, 53.85, H, 9.65, N,9.74, F, 17.88, Br, undetectable. Analytical data suggests that fluorideis in the form of the H₂ F₃ ⁻ anion.

EXAMPLE 4 Hexyl monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with hexyl bromide. The product,3-(methacryloylamino)propyldimethylhexylammonium polyhydrogenfluoride-fluoride monomer, was a crystalline solid having a meltingpoint of 115°-120° C. ¹ H-NMR analysis yielded the following results:(Solvent: CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H, CH₂ ═), 3.4 (m, 6H, NCH₂), 3.1(s, 6H, N(CH₃)₂), 2.0 (m, 2H, --CH₂ --) , 1.95 (s, 3H, --CH₃ ) , 1.7(broad s, 2H, NCH₂ --CH₂), 1.4 (s, 6H, --(CH₂)₃), 1.9 (t, 3H, CH₃), ¹³C: δ --0.02, 14.2, 18.7, 23.5, 23.8, 27.1, 32.5, 37.4, 37,6, 51.4,;62.8, 65.2, 121.1, 140.9, 171.4. Elemental analysis: Found C, 54.94, H,9.85, N, 8.68, F, 17.51, Br, undetectable. Analytical data suggests thatfluoride is in the form of the H₂ F₃ ⁻⁻ anion.

EXAMPLE 5 Octyl monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with octyl bromide. The resulting product, 3-(methacryloylamino)propyldimethyloctylammonium polyhydrogenfluoride-fluoride monomer, was a crystalline solid having a meltingpoint of 118°-121° C. ¹ H-NMR analysis yielded the following results:(Solvent: CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H, CH₂ ═), 3.4 (m, 6H, NCH₂ --),3.1 (s, 6H, N(CH₃)₂), 2.0 (m, 2H, --CH₂ --), 1.95 (s, 3H, CH₃), 1.7(broad s, 2H, NCH₂ --CH₂ --) , 1.4 (d, 10H, --(CH₂)₃ --)₂) , 0.9 (t, 3H,CH₃), ¹³ C: δ 0.05, 14.4, 14.5, 18.8, 23.6, 23.8, 27.4, 30.3, 32.9,37.6, 51.4, 62.9, 65.2, 121.1, 140.9, 171.4.

EXAMPLE 6 Decyl Monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with decyl bromide. The product,3-(methacryloylamino)propyldimethyldecylammonium polyhydrogenfluoride-fluoride, was a crystalline solid having a melting point of122°-126° C. ¹ H-NMR analysis yielded the following results: (Solvent:CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H, CH₂ ═), 3.4 (m, 6H, NCH₂ --), 3.1 (S,6H, N(CH₃)₂) 3.4 (m, 6H, NCH₂ --), 3.1 (s, 6H, N(CH₃)₂), 2.0 (m, 2H,--CH₂ --), 1.95 (2, 3H, CH₃), ¹³ C: δ 0.03, 14.7, 14.8, 19.1, 23.8,24.1, 27.7, 30.6, 30.7, 30.9, 33.1, 37.8, 51.7, 63.2, 65.5, 121.4,141.2, 171.6.

EXAMPLE 7 Acetamido monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with 2-bromoacetamide. The product,3-(methacryloylamino)propyldimethylacetamidoammonium polyhydrogenfluoride-fluoride monomer, was a crystalline solid having a meltingpoint of 250° C.:(d). ¹ H-NMR analysis yielded the following results:(Solvent: CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H, CH₂ ═), 4.2, 3.6, 3.4 (s, m,m, 6H, NCH₂ --), 3.3 (s, 6H, N(CH₃)₂), 2.1 (m, 2H, --CH₂ --), 1.9 (s,3H, CH₃), ¹³ C: δ 18.8, 23.9, 27.5, 52.3, 62.8, 64.4, 120.9, 140.9,167.6, 171.3. Elemental analysis: Found C, 42.84, H, 7.39, N, 13.54, F,20.67, Br, undetectable. Analytical data suggests that fluoride is inthe form of the H₂ F₃ -- anion.

EXAMPLE 8 Hydroxyethyl monomer

The preparative procedure of Example 1 was repeated, except replacingdodecyl bromide with hydroxyethyl bromide. The resulting product,3-(methacryloylamino)propyldimethylhydroxyethylammonium polyhydrogenfluoride-fluoride, was a non-crystalline waxy solid. ¹ H-NMR analysisyielded the following results: (Solvent: CD₃ OD) ¹ H: δ 5.8, 5.4 (s, 2H,CH₂ ═), 4.0, 3.4, 3.35 (m, 6H, NCH₂ --), 3.2 (s, 6H, N(CH₃)₂), 2.1 (m,2H, --CH₂ --), 1.95 (s, 3H, CH₃), ¹³ C: δ 18.8, 23.9, 37.6, 52.3, 47.0,64.4, 66.5, 121.0, 141.0, 171.4.

EXAMPLE 9 Tetramethylene difluoride cross-linker

A tetramethylene difluoride cross-linker, specifically1,4-bis-[3-(methacryloylamino)propyldimethylammonium]butane difluoride,was prepared as follows. A mixture of3-(methacryloylamino)propyldimethylamine (9.37 g, 0.055 mol) and1,4-dibromobutane (5.40 g, 0.025 mol) in acetonitrile (50 ml) wasstirred at room temperature for 48 hours. The bis-quaternary ammoniumdibromide was collected by filtration after crystalization fromacetonitrile in 94.5% yield, mp 149.5°-150° C.

Fluoride ion-exchange was performed by two methods:

1) The dibromide salt was treated with an equivalent amount of AgF inmethanol at room temperature. The difluoride product was obtained afterfiltration to remove AgBr and evaporation under reduced pressure of thefiltrate. Further purification was achieved by recrystallization fromacetonitrile.

2) A methanol solution of the dibromide salt was passed through a columnpacked with the F⁻⁻ form of Amerlite IRA-400 ion-exchange resin. Thedifluoride product was obtained by the procedure described in Example 1.The ion-exchange resin was loaded with fluoride ion by the followingprocedure. The commercial IRA-400 (Cl⁻⁻ form) resin was first convertedto its OH⁻⁻ form by washing with a 5% aqueous NaOH solution until nochloride ion could be detected in the effluent with acidic AgNO₃solution, followed by rinsing the resin bed with water until neutral topH paper. Then, the OH⁻⁻ form of IRA-400 resin was converted to fluorideform by passing a 4% aqueous NaF solution until the pH value of theeffluent was the same as that of NaF solution (˜7.5), followed byrinsing the resin bed with water until neutral to pH paper. The IRA-400(F⁻⁻) resin suspension in water was filtered and washed with methanol.

The resulting difluoride cross-linker is a crystalline solid with amelting point of 160° C (d). ¹ H-NMR analysis yielded the followingresults. (Solvent, D20) ¹ H: δ 5.75, 5.42 (S, 4H, CH₂ ═), 3.30-3.45 (m,12H, --NCH₂ --), 3.11 (S, 12H, --N(CH₃)₂, 2.00-2.15 (m, 4H --CH₂ --),1.95 (S, 6H, --C═C(CH₃)--), 1.80-1.90 (m, 4H, --CH₂ --). Elementalanalysis, Found (%), C, 56.04, H, 10, 15, N, 11.87, F. 7.85. Analyticaldata suggests that fluoride is in the form of the F⁻⁻ anion.

EXAMPLES 10-11

The preparative procedure of Example 9 was repeated, except replacing1,4-dibromobutane with bromoethane or bromoacetamide. Analytical datasuggests that the resulting fluorides,3-(methacryloylamino)propylethyldimethylammonium fluoride and3-(methacryloylamino)propyldimethylacetamidoammonium fluoride, are inthe form of the F⁻⁻ anion.

EXAMPLE 12 Methyl fluoride monomer

3-(Methacryloylamino)propyltrimethylammonium chloride (Aldrich) wasion-exchanged with IRA-400 (F) in water or in methanol using theprocedures of Example 9. The resulting fluoride salt is a crystallinesolid having a melting point of 110°-113° C. (d). ¹ H-NMR analysisyields the following results (solvent D₂ O) ¹ H: δ5.70, 5.46 (S, 2H, CH₂═), 3.33-3.36 (m, 4H, --N CH₂ --) 3.11 (S, 9H, --N(CH₃)3), 2.05-2.06 (m,2H, --CH₂ --), 1.92 (S, 3H, C═C--CH₃). Elemental analysis, Found (%):C,53.43, H, 10.15, N, 12.38, F, 8.25. Analytical data suggest that thefluoride is in the form of the F⁻⁻ artion.

EXAMPLE 13 Resin Formulation with Dodecyl Monomer

A resin for testing fluoride release was prepared according to theformulation given in Table 1.

                  TABLE 1                                                         ______________________________________                                        Component             Part A    Part B                                        ______________________________________                                        Methacrylic Acid      0.75 ml   0.75 ml                                       Trimethylpropanetrimethacrylate                                                                     0.75 ml   0.75 ml                                       Ethyleneglycol dimethacrylate                                                                       2.15 ml   2.15 ml                                       Fluoride Monomer of Ex. 1                                                                           130 mg    130 mg                                        Benzoyl peroxide       20 mg    --                                            N,N-Dimethyl p-toluidine                                                                            --         10 mg                                        MEHQ                  200 ppm   200 ppm                                       ______________________________________                                    

After mixing together parts A and B in a disk die, an exothermic curingoccurred. The specimens of resin in the form of disk samples (10 mmdiameter×3 mm thick) were evaluated for average daily fluoride ionrelease over a thirty day period (μg/cm² /day) alongside commerciallyavailable materials, by suspending the disks in deionized water andmeasuring the accumulation of fluoride ion over time using anion-specific electrode. The results are set forth in Table 2.

                  TABLE 2                                                         ______________________________________                                        Material         Release                                                      ______________________________________                                        Inventive Resin  6.5                                                          Fluoroever       1.4                                                          Fluorocore       1.5                                                          FluoroShield     0.4                                                          AllBond Linear-F 0.2                                                          ______________________________________                                    

EXAMPLES 14-15 Resin Formulation with Ethyl Monomer

Resin disks were prepared as in Example 13, except incorporating theethyl monomer of Example 2 according to the formulation given in Table3.

                  TABLE 3                                                         ______________________________________                                        Component             Part A    Part B                                        ______________________________________                                        Methacrylic Acid      0.25 ml   0.25 ml                                       Trimethylpropanetrimethacrylate                                                                     0.25 ml   0.25 ml                                       Ethyleneglycol dimethacrylate                                                                       0.75 ml   0.75 ml                                       Fluoride Monomer B    *         --                                            Benzoyl peroxide      20 mg     --                                            N,N-Dimethyl p-toluidine                                                                            --        10 mg                                         ______________________________________                                         * Two samples were prepared, one with 183 mg (4.9% W/W, Example 11) and       one with 345 mg (9.0% W/W, Example 12).                                  

The hardness of the resins was tested with a Knoop Hardness apparatus.The resin of Example 11 exhibited a Knoop hardness of 22, while that ofExample 12 exhibited a Knoop hardness of 16. Importantly, the fluoriderelease data indicate that the resins sustain fluoride release at alevel (˜10μg/cm₂ /day) approximately equivalent to that of Fuji II, afluoride-containing ionomer. The resins also demonstrated significantlyimproved hardness compared to the resin prepared with the dodecylmonomer of Example 13.

EXAMPLES 16-29 Resin Formulations

Additional resins were prepared using the general procedures and each ofthe fluoride containing monomers ("F-Monomers") described in theExamples above, loaded to 5% to 7.5% in each of Parts A and B, assummarized in Tables 4 and 5.

                  TABLE 4                                                         ______________________________________                                        Component          Part A     Part B                                          ______________________________________                                        bis-phenol-A-Glycidyl methacrylate                                                               23.1%      23.1%                                           triethylene glycol dimethacrylate                                                                33.4%      33.4%                                           methacrylic acid   3.15%      3.15%                                           benzoyl peroxide   0.25%      --                                              N,N-dimethyl-p-toluidine                                                                         --         0.11%                                           F-Monomer          5%-7.5%-   5%-7.5%-                                        Microfiller*(coupling agent**)                                                                   27%        27%                                             Microfiller*       7.5%-5%    7.5%-5%                                         ______________________________________                                         *Degussa AEROSIL 130 microfiller                                              **Denotes microfiller treated with 3methacryloyloxypropyl-trimethoxy          silane                                                                   

                  TABLE 5                                                         ______________________________________                                        Example    Monomer of   Part A  Part B                                        ______________________________________                                        16         Example 2      5%      5%                                          17         Example 3    7.5%    7.5%                                          18         Example 4    7.5%    7.5%                                          19         Example 5    7.5%    7.5%                                          20         Example 6    7.5%    7.5%                                          21         Example 1      5%      5%                                          22         Example 1    7.5%    7.5%                                          23         Example 7    7.5%    7.5%                                          24         Example 9    7.0%    7.0%                                          25         Example 10   7.0%    7.0%                                          26         Example 12   7.0%    7.0%                                          ______________________________________                                    

In addition, the monomer of Example 1 was used to prepare similarformulations loaded to 10% (Example 27) and 20% (Example 28) in Parts Aand B by increasing the amount of monomer used. Similarly, the monomerof Example 7 was used to prepare an additional formulation loaded to 10%(Example 29). In each case, resins were formed which release fluorideover time.

EXAMPLES 30-31 Evaluation of Adhesive Properties

The resins of Examples 18 and 19 were evaluated for tensile bondstrength compared to Phase IIT (Reliance Orthodontic Products, Itasca,Ill.), a commercially available, fluoride-free two paste chemical cureresin adhesive used for orthodontic bonding. Tensile bond strengthtesting utilized commercially available stainless steel brackets fromOrmco Orthodontics (Glendora, Calif.). The brackets were designed formaxillary central incisors, had no torque or angularion, and had meshbacked bases. The brackets were bonded to 51 bovine incisors using theresins of Examples 18 and 19. The teeth were first examined visually anddetermined to be free of gross irregularities, enamel cracks, or debris.They were then prepared for bonding by first removing the roots at thecemento-enamel junction and extraneous mesial, distal, and incisalareas. Only the middle third of the labial surface was utilized forbonding. The facial surfaces were flattened by grinding with coarse andfine grit sicpaper under running water, and each tooth was embedded in aself-curing epoxy resin. Comparison of the inventive and control resinsby ANOVA followed by General Linear Models multiple comparisons revealedthat the resins of Examples 18 and 19 had bond strengths of 4.45±0.65MPA and 3.83±0.76 MPa, respectively, and the control had a bond strengthof 5.31±0.97 MPa.

While the invention has been described above in some detail, it will beunderstood that certain modifications and variations can be made withoutdeparting from the spirit and scope thereof.

What is claimed is:
 1. A polymerizable fluoride ion-releasing monomerhaving the formula (I): ##STR9## wherein Y⁻⁻ is a fluoride-containinganion of the formula ((HF)_(x) F)⁻⁻ wherein x=1 to 7, R¹ is --H ormethyl, R² is a divalent C₁ -C₁₂ alkylene radical, and each R³, whichmay be the same as or may differ from one another, is H, C₁ -C₁₆ alkylor hydroxyalkyl, or a group of the formula ##STR10## wherein R¹, R² andR³ are as defined above, n is an integer from 1 to about 12, and eachR⁴, which may be the same as or may differ from one another, is H, loweralkyl, lower hydroxyalkyl, or an amide group of the formula --CH(CH₂OH)(CONHCH₂ CH₂ OH).
 2. The monomer of claim 1 wherein R¹ is methyl. 3.The monomer of claim 1 wherein each R³, which may be the same as or maydiffer from one another, is C₁ to C₁₆ alkyl.
 4. The monomer of claim 1wherein two of said groups R³ are lower alkyl and the third group R³ isa group of the formula ##STR11## wherein R¹ is as defined in claim
 1. 5.The monomer of claim 1 wherein R² is --(CH₂)_(m) -- wherein m=is aninteger from 2 to
 6. 6. The monomer of claim 1 wherein each group R³ islower alkyl.
 7. The monomer of claim 1 wherein Y⁻⁻ is (HF)_(x) F)--wherein x=2 to
 3. 8. The monomer of claim 1, wherein R¹ is --CH₃, R² is--(CH₂)₃ --, and each group R³ is lower alkyl.
 9. The monomer of claim 1wherein R¹ is --CH₃, R² is --(CH₂)₃ --, and at least one group R³ is##STR12## wherein R¹ is as defined in claim
 1. 10. A process forpreparing a polymerizable fluoride ion-containing monomer,comprising:reacting a compound of the formula: ##STR13## with a compoundof the formula R³ --L, wherein R¹ is --H or methyl, R² is a divalent C₁-C₁₂ alkylene radical, L is a leaving group, and each R³, which may bethe same as or may differ from one another, is H, C₁ -C₁₆ alkyl, or agroup of the formula ##STR14## wherein R¹, R² and R³ are as definedabove, n is an integer from 1 to about 12, and each R⁴, which may be thesame as or may differ from one another, is H, lower alkyl, lowerhydroxyalkyl, or an amide group of the formula --CH(CH₂ OH)(CONHCH₂ CH₂OH); to form a compound of the formula: ##STR15## and exchanging L⁻⁻ fora fluoride-containing anion of the formula ((HF)_(x) F)⁻⁻ wherein x=1 to7.
 11. The process of claim 10 wherein L⁻⁻ in formula (VI) is exchangedfor a fluoride-containing anion of the formula wherein x=1 to
 7. 12. Theprocess of claim 11 wherein each R³ is C₁ to C₁₆ alkyl.
 13. The processof claim 11 wherein at least one group R³ is a group of the formula##STR16##
 14. The process of claim 11 wherein at least one group R³ is agroup of the formula ##STR17##
 15. The process of claim 11 wherein R¹ is--CH₃, R² is --(CH₂)₃ --, and each group R³ is lower alkyl.
 16. Theprocess of claim 15 wherein two groups R³ are methyl and the third groupR³ is ethyl.
 17. The process of claim 11 wherein two groups R³ are loweralkyl and the third group R³ is a group of the formula ##STR18## whereinn is an integer from 1 to about 12, and each R⁴, which may be the sameas or may differ from one another, is H, lower alkyl, lowerhydroxyalkyl, or an amide group of the formula --CH(CH₂ OH)(CONHCH₂ CH₂OH).
 18. The process of claim 17 wherein each R⁴ is H.
 19. The processof claim 10 wherein L is a leaving group selected from Cl, Br, I, andSO₃ R wherein R is alkyl, aryl or alkyl-aryl.
 20. A fluorideion-releasing acrylic or methacrylic polymerizable monomer bearing ananion exchange site carrying a fluoride-containing anion of the formula(HF)_(x) F)⁻⁻ wherein x is an integer from 1 to
 7. 21. The monomer ofclaim 20 which is an acrylate, methacrylate, acrylamide ormethacrylamide monomer.
 22. The monomer of claim 21 wherein x is 2 or 3.23. A polymerizable fluoride ion-releasing monomer having the formula(I): ##STR19## wherein Y⁻⁻ is a fluoride or fluoride-containing anion,R¹ is --H or methyl, R² is a divalent C₁ -C₁₂ alkylene radical, and eachR³, which may be the same as or may differ from one another, is H, C₁-C₁₆ alkyl or hydroxyalkyl, or a group of the formula ##STR20## whereinR¹, R² and R³ are as defined above, n is an integer from 1 to about 12,and each R⁴, which may be the same as or may differ from one another, isH, lower alkyl, lower hydroxyalkyl, or an amide group of the formula--CH(CH₂ OH)(CONHCH₂ CH₂ OH), with the proviso that at least one groupR³ is of the formula (II), (III) or (IV).
 24. The monomer of claim 23,wherein only one group R³ is of the formula (II), (III) or (IV).
 25. Themonomer of claim 23, wherein said only one group is of the formula (II)or (III) and each of the remaining groups R³ is lower alkyl.
 26. Themonomer of claim 25, wherein said only one group is of the formula (II),and R² is --(CH₂)_(m) -- wherein m is an integer from 2 to
 6. 27. Themonomer of claim 25, wherein said only one group is of the formula(III), and R² is --(CH₂)_(m) -- wherein m is an integer from 2 to
 6. 28.A monomeric admixture suitable for preparing a dental resin,comprising:a fluoride ion-releasing polymerizable acrylamide ormethacrylamide monomer of formula (I) ##STR21## wherein Y⁻⁻ is afluoride or fluoride-containing anion, R¹ is --H or methyl, R² is adivalent C₁ -C₁₂ alkylene radical, and each R³, which may be the same asor may differ from one another, is H, C₁ -C₁₆ alkyl or hydroxyalkyl, ora group of the formula ##STR22## wherein R¹, R² and R³ are as definedabove, n is an integer from 1 to about 12, and each R⁴, which may be thesame as or may differ from one another, is H, lower alkyl, lowerhydroxyalkyl, or an amide group of the formula --CH(CH₂ OH)(CONHCH₂ CH₂OH), in admixture with at least one other polymerizable acrylic ormethacrylic monomer, with the proviso that at least one of said monomersis a free-radical initiated crosslinking monomer.
 29. The monomericadmixture of claim 28, which includes a fluoride ion-releasingacrylamide or methacrylamide crosslinking monomer.
 30. The monomericadmixture of claim 29, in which said at least one other acrylic ormethacrylic monomer is an acrylate, methacrylate, acrylamide ormethacrylamide monomer.
 31. The monomeric admixture of claim 28, whereinsaid fluoride ion-releasing polymerizable acrylamide or methacrylamidemonomer carries an anion of the formula ((HF)_(x) F)⁻⁻ wherein x is aninteger from 1 to
 7. 32. A monomeric admixture suitable for preparing adental resin, comprising:a fluoride ion-releasing polymerizable acrylicor methacrylic monomer in admixture with at least one otherpolymerizable acrylic or methacrylic monomer, said fluoride ionreleasing polymerizable monomer bearing an anion exchange site carryinga fluoride-containing anion of the formula ((HF)_(x) F)⁻⁻ wherein x isan integer from 1 tro 7, with the proviso that at least one of saidmonomers is a crosslinking monomer.